Pancreatic cancer is one of the hardest cancers to treat; tumors of the pancreas often fail to respond to current therapies. In a new study, researchers reveal how they may have found a way to boost the treatment response of these tumors.
Published in the journal Nature Medicine, the study reveals how administering a drug called a focal adhesion kinase (FAK) inhibitor to pancreatic cancer mouse models significantly improved tumor response to chemotherapy and immunotherapy, increasing the rodents’ survival rate.
Senior author David G. DeNardo, Ph.D., an assistant professor of medicine at the Washington University School of Medicine, and colleagues now plan to test this drug combination in humans with advanced pancreatic cancer, with the hope it will significantly improve patient outcomes.
According to the American Cancer Society, around 53,070 people in the United States will be diagnosed with pancreatic cancer in 2016, and more than 41,000 people will die from the disease.
The survival rate for pancreatic cancer is low, with only around 7.7 percent of patients surviving 5 years or more after diagnosis.
“Pancreatic tumors are notoriously unresponsive to both conventional chemotherapy and newer forms of immunotherapeutics,” notes DeNardo.
“We suspect that the fibrous environment of the tumor that is typical of pancreatic cancer may be responsible for the poor response to immune therapies that have been effective in other types of cancer.”
DeNardo further explains that FAK’s are known to play a role in the development of fibrous tissue in cancer and a number of other diseases.
Fibrous tissue protects cancer cells by preventing the immune system from attacking them. This stops the cancer cells from entering the bloodstream, which reduces their exposure to chemotherapy.
With this in mind, he and his colleagues set out to determine whether inhibiting the FAK pathway might halt the development of fibrous tissue, and therefore make tumors more responsive to treatments.
‘Three-pronged approach’ tripled survival of mice
For their study, mice with pancreatic tumors were given either chemotherapy alone, immunotherapy alone, an FAK inhibitor alone, a combination of chemotherapy or immunotherapy with an FAK inhibitor, or a combination of all three treatments.
Adding an FAK inhibitor to immunotherapy appeared to have no impact on the survival of the mice, the researchers report.
Compared with mice that received chemotherapy alone, those that received a combination of immunotherapy and the FAK inhibitor demonstrated an increased tumor response.
However, the mice that received a combination of all three treatments – the FAK inhibitor, immunotherapy, and chemotherapy – showed a much greater tumor response; survival more than tripled for some of the rodents, and at 6 months after treatment, these mice showed no signs of disease progression.
Based on their findings, the researchers suggest adding FAK inhibitors to chemotherapy and immunotherapy has the potential to improve outcomes for patients with pancreatic cancer, and they now plan to test this approach in the phase I clinical trial.
"We hope to improve outcomes for these patients, especially since survival with metastatic pancreatic cancer is typically only 6 months to a year.The advantage of our three-pronged approach is that we are attacking the cancer in multiple ways, breaking up the fibers of the tumor micro environment so that more immune cells and more of the chemotherapy drug can attack the tumor." Co-author Dr. Andrea Wang-Gillam, Washington University School of Medicine